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Phase 1/1b Study of Oral PMD-026 in Patients With Metastatic Breast Cancer and Metastatic Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT04115306
Recruitment Status : Not yet recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Phoenix Molecular Designs

Brief Summary:
The purpose of this study is to test the safety and tolerability of PMD-026 in patients with metastatic breast cancer and triple negative breast cancer. PMD-026 is a targeted oral agent designed to kill tumor cells in metastatic breast cancer and triple negative breast cancer.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Triple Negative Breast Cancer Drug: PMD-026 Phase 1

Detailed Description:

This study will evaluate the safety and tolerability of PMD-026 using an accelerated titration design to define the MTD in metastatic breast cancer, followed by an expansion at the RP2D in triple negative breast cancer. All patients will receive daily oral doses of PMD-026 until either disease progression or unacceptable toxicity. Patients will have disease assessments initially after 6 weeks of treatment, and every 9 weeks thereafter.

Patients enrolled to the Dose Escalation Phase must have histologically or cytologically diagnosed metastatic breast cancer that has progressed on or after standard of care therapy. Patients enrolled to the Dose Expansion Phase must have histologically or cytologically diagnosed metastatic triple negative breast cancer that has progressed on or after standard of care therapy. All patients must provide tumor tissue (archival preferred) prior to study entry.

PMD-026 is an oral, reversible small molecule inhibitor of RSK1-4 with high selectivity for RSK2. High levels of RSK2 expression have been associated with worse overall survival in breast cancer. Inhibiting RSK2 may inhibit growth of breast cancer.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/1b Multicenter, Open-Label, First-in-Human Dose Escalation and Dose Expansion Study to Assess Safety and Tolerability of Orally Administered PMD-026 in Patients With Metastatic Breast Cancer With Expansion in Metastatic Triple Negative Breast Cancer
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: PMD-026
Oral PMD-026 (dose: 25 - 1000 mg), given daily until disease progression or unacceptable toxicity
Drug: PMD-026
Oral RSK1-4 inhibitor




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Through study completion, an average of 12 weeks ]
    Toxicities will be assessed in each patient by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0.

  2. Maximum tolerated dose (MTD) of PMD-026 [ Time Frame: Up to 21 days ]
    The MTD will be defined as the dose level at which no more than one of six patients experiences a dose limiting toxicity (DLT) after 21 days of treatment have occurred, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.

  3. Recommended Phase 2 Dose (RP2D) of PMD-026 [ Time Frame: Up to 14 months ]
    The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee.

  4. Efficacy in Patients [ Time Frame: 6 weeks ]
    Anti-tumor activity (efficacy) will be assessed in all patients.


Secondary Outcome Measures :
  1. Plasma Concentration [ Time Frame: 24 hours ]
    The plasma concentration will be measured as part of pharmacokinetic (PK) testing.

  2. Time to Response [ Time Frame: 6 weeks ]
    The time to response will be evaluated by disease assessments.

  3. Duration of Response [ Time Frame: 6 weeks ]
    The duration of response will be evaluated by disease assessments from time of first response (CR or PR) to time of disease progression.


Other Outcome Measures:
  1. RSK2 Expression [ Time Frame: 6 weeks ]
    RSK2 expression will be evaluated in breast cancer tissue through immunohistochemistry (IHC).

  2. PMD-026 Activity in Tissue [ Time Frame: 6 weeks ]
    PMD-026 activity will be evaluated in Lehmann subtypes in breast cancer tissue.

  3. RSK2 Expression and Response [ Time Frame: 12 weeks ]
    The relationship between RSK2 expression and response will be evaluated following RSK2 IHC and disease assessments.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent
  2. Age ≥ 18 years
  3. ECOG Performance Status ≤ 2
  4. [Part 1 - Dose Escalation] Histologically or cytologically diagnosed metastatic breast cancer that has progressed on or after standard of care therapy and for which no standard of care therapy is available that would confer clinical benefit
  5. [Part 2 - Dose Expansion] Histologically or cytologically diagnosed metastatic triple-negative breast cancer that has progressed on or after standard of care therapy and for which no standard of care therapy is available that would confer clinical benefit
  6. [Part 1 - Dose Escalation] Evaluable or measurable disease by RECISTv1.1
  7. [Part 2 - Dose Expansion] Measurable disease by RECISTv1.1
  8. Adequate laboratory parameters including:

    1. Absolute Neutrophil Count (ANC) ≥ 1500/mm^3
    2. Platelets ≥ 100,000/mm^3
    3. AST/SGOT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
    4. ALT/SGPT ≤ 2.5 x ULN (≤ 5 x ULN if known liver involvement)
    5. Total bilirubin ≤ 1.5 x ULN (unless diagnosis of Gilbert's syndrome in which case < 3.0 times ULN)
    6. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 60 mL/min
  9. If residual treatment related toxicity from prior therapy:

    1. Treatment related toxicity resolved to at least Grade 1 (alopecia excepted), or
    2. Treatment related toxicity resolved to at least Grade 2 with prior approval of the Medical Monitor
  10. Available archival or fresh tumor tissue (Formalin-fixed paraffin-embedded [FFPE])
  11. [Females] The patient must be postmenopausal, surgically sterile, or agree to use adequate contraception (adequate as determined by the PI - may include abstinence) throughout the study and for a least 30 days following the last dose of PMD-026
  12. [Males] The patient must be surgically sterile or must agree to use adequate contraception (adequate as determined by the PI - may include abstinence) throughout the study and for at least 30 days following the last dose of PMD-026
  13. [Males] The patient must agree to refrain from donating sperm throughout the study and for at least 30 days following the last dose of PMD-026
  14. [Females] If of childbearing potential, the patient must have a negative serum pregnancy test

Exclusion Criteria:

  1. ≤ 14 days from prior chemotherapy, biological or investigational therapy
  2. Use of any medications known to result in a prolongation of the QT/QTc interval
  3. Use of any medication that is a strong inducer or substrate of cytochrome P450 3A
  4. Use of any medications that is a substrate of BCRP
  5. Use of any medication that is a substrate of MATE2K
  6. ≤ 28 days from prior irradiation (including therapeutic radioisotopes such as strontium 89)
  7. ≤ 7 days from limited field irradiation for palliation
  8. ≤ 28 days from major surgical procedures
  9. ≤ 7 days from minor surgical procedures (no waiting period required following central catheter placement)
  10. Central nervous system metastases, unless appropriately treated and neurologically stable for ≥ 28 days
  11. Known history of leptomeningeal metastases
  12. Uncontrolled bacterial, viral, or fungal infection (s) requiring systemic therapy
  13. Pregnant or currently breast-feeding
  14. Known Hepatitis B or Hepatitis C infection
  15. Known HIV-positive with CD4+ cell counts < 350 cells/uL
  16. Known HIV-positive with a history of an AIDS-defining opportunistic infection
  17. History of clinically significant cardiovascular abnormalities including:

    1. Congestive heart failure (NYHA classification ≥ 3 in within 6 months of first dose of PMD-026
    2. Unstable angina pectoris
    3. Myocardial infarction within 12 months of study entry
    4. Arrhythmias requiring continued treatment (controlled atrial fibrillation allowed)
    5. QTcF interval > 460 msec (using Fridericia's formula)
  18. Presence of active gastrointestinal disease or other condition that is expected to interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥ 2, and malabsorption syndrome)
  19. Inadequately controlled hypertension defined as systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg (patients with values above these levels must have their blood pressure controlled prior to starting treatment)
  20. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment
  21. Other known active cancer(s) likely to require treatment in the next year that would impact the assessment of any study endpoints
  22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04115306


Contacts
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Contact: Kaitlyn Cohen 858-642-0386 ext 205 kcohen@sciquus.com

Sponsors and Collaborators
Phoenix Molecular Designs

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Responsible Party: Phoenix Molecular Designs
ClinicalTrials.gov Identifier: NCT04115306     History of Changes
Other Study ID Numbers: PMD-026-1-001
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases